They manage to break molecular symmetry

Scientists have managed to synthesize molecules with a special type of molecular asymmetry.

The Metal Catalysis and Organocatalysis Research Group of the University of the Basque Country (UPV/EHU), in collaboration with the Rovira i Virgili University of Tarragona, has developed a methodology to desymmetrize certain molecules and obtain a type of molecular asymmetry that opens the door to new structures unprecedented in nature and that could be used as therapeutic agents.

The group is led by UPV/EHU professor José Luis Vicario.

The group, which works on asymmetric synthesis of small organic molecules, has managed to “synthesize intrinsically asymmetric cyclic molecules using catalysis. “We have developed an effective and direct methodology, using small amounts of a catalyst derived from copper, an abundant and non-harmful metal,” says the Professor of Organic Chemistry at the UPV/EHU.

The vast majority of organic molecules (based on a carbon structure) are not planar; They have three-dimensional geometry. Depending on the way the atoms are arranged within each molecule, results can be obtained. In some cases a molecule and its mirror image (that is, two symmetrical molecules that have the same relationship as an object has with its image in a mirror) can have completely different properties.

Let’s use the simile of hands to explain it: our hands are mirror images of each other; It can be said that they are identical. However, when one hand is placed on top of the other (not in a position of putting the palms together, but rather overlapping one hand on the other), the position of the fingers is not the same. The same thing happens with some molecules, the organization of the atoms does not coincide. Each of the mirror images of a molecule that are not superimposable is called an enantiomer.

“In nature and in pharmacology there are many examples in which the two enantiomers have different properties. This is the case of thalidomide (a drug administered as a sedative and nausea reliever during the first three months of pregnancy, which caused thousands of cases of congenital malformations), one of the enantiomers has analgesic properties and the other produces malformations —explains Efraim. Reyes, from the UPV/EHU and one of the main authors of the work. This occurs because therapeutic targets do not interact in the same way with one enantiomer or another. Therefore, it is essential to control the synthesis of this type of molecules, to obtain only one of the two enantiomers.”

Predoctoral researcher Josebe Hurtado has been able to selectively construct one of the two enantiomeric molecules of a group of cyclobutanes (cyclic molecules that essentially contain carbon and hydrogen atoms), “through desymmetrization; that is, breaking the planar symmetry and converting them into elementary synthetic blocks of more complex molecules,” explains his thesis director Efraim Reyes.

Josebe Hurtado. (Photo: Laura López, Communication Office, UPV/EHU)

This achievement responds to a great current challenge and a research area of ​​growing interest. “We have managed to synthesize molecules with an axial asymmetry (supported by an axis), which has no precedent in nature and which opens a door to the study of a new type of molecules, which can also be used to develop new therapeutic avenues,” adds Vicario. . Furthermore, through strict control of the reactions “we have broken the planar symmetry to convert it into axial asymmetry and then into punctual asymmetry (supported at one point),” explains the UPV/EHU professor. This shows “that there is a real possibility that biomolecules with asymmetry may also have a common origin.”

Spontaneous desymmetrization, origin of life

This finding is reminiscent of one of the theories related to the origin of life, which is based on the fact that through a spontaneous desymmetrization of symmetry, the molecules that gave rise to life were formed. “One of the theories of the origin of life, widely accepted, says that originally there were only symmetrical molecules and that through a process of spontaneous desymmetrization, asymmetric molecules emerged, which are evidently the origin of life, because our entire organism and living systems They are based on biomolecules that are asymmetric and only contain one of the two enantiomers,” concludes Reyes.

This research has been carried out within the framework of Josebe Hurtado’s doctoral thesis and in collaboration with the research group led by the Rovira i Virgili University professor Elena Fernández.

The study is titled “Cu-Catalyzed Enantioselective Borylative Desymmetrization of 1-Vinyl Cyclobutanols and Axial-to-Point Chirality Transfer in a Diastereoconvergent/Stereoretentive Allylation Scenery.” And it has been published in the academic journal Angewandte Chemie. (Source: UPV/EHU)